Expense, availability and/or incomplete acceptance based upon an unfounded fear of infection with the agents of AIDS limit the impact of plasma-derived hepatitis B vaccines in developed and developing countries. There is therefore a need for new approaches to vaccine development. Recombinant DNA and synthetic peptide technologies appear to offer the best opportunities for the next generation of hepatitis B vaccines. Partial or complete protection against hepatitis B has been demonstrated in chimpanzees following vaccination with (a) recombinant derived subunit vaccine prepared in eukaryotic cells, (b) live recombinant vaccinia virus containing HBV genes, and (c) synthetic peptides representing HBsAg sequences. Attempts to identify the antigenic domains most important in stimulating neutralizing antibody are currently in progress.